Abstract
Since 1988, the National Cholesterol Education Program has identified low-density lipoprotein cholesterol (LDL-C) as the target of therapy; the new Adult Treatment Panel III (ATP III) guidelines continue the tradition of matching the aggressiveness of LDL-lowering therapy according to the risk of coronary heart disease (CHD). A significant change in the new guidelines is the definition of.CHD risk equivalents. and the inclusion of a modified Framingham global risk score. These revisions significantly raise the number of patients who qualify for lipid-lowering therapy. ATP III recognizes statins as the drug of first choice for LDL-C lowering. Statins are proven to be safe and effective for LDL-C reduction and are proven to reduce CHD event rates and mortality. Some patients are not candidates for statin therapy, however, and must rely on nonstatin agents that are less effective in reducing LDL-C, less safe, or poorly tolerated. Consequently, new cholesterol-lowering therapies are needed. Ezetimibe, approved by the U.S. Food and Drug Administration (FDA) in October 2002, is the first in a new class of selective cholesterol absorption inhibitors and offers a novel approach to the treatment of dyslipidemia. Phase 2 data demonstrated that ezetimibe lowers LDL-C by 18% and has a tolerability and short-term safety profile similar to placebo. This paper reviews the cholesterol metabolic pathways and the mechanism of action of the currently available lipid-modifying agents and introduces ezetimibe, the first selective cholesterol absorption inhibitor.
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